Despite reports of high levels of violence among women migrants in Central America, limited evidence exists regarding the health and safety of migrant sex workers in Central America. This study is based on 16 months of field research (November 2012–February 2015), including ethnographic fieldwork, in-depth interviews, and focus groups conducted with 52 internal and international migrant female sex workers in Tecún Úman and Quetzaltenango, Guatemala, key transit and destination communities for both international and internal migrants. The analysis explored migration-related determinants of susceptibility to violence experienced by migrant sex workers across different phases of migration. Violence in home communities and economic considerations were key drivers of migration. Unsafe transit experiences (e.g., undocumented border crossings) and negative interactions with authorities in destination settings (e.g., extortion) contributed to migrant sex workers’ susceptibility to violence, while enhanced access to information on immigration policies and greater migration and sex work experience were found to enhance agency and resilience. Findings suggest an urgent need for actions that promote migrant sex workers’ safety in communities of origin, transit, and destination, and programmes aimed at preventing and addressing human rights violations within the context of migration and sex work.